Human CDH1 Recombinant Protein (RPPB3126)

Subunit structure: Homodimer; disulfide-linked. Component of an E-cadherin/ catenin adhesion complex composed of at least E-cadherin/CDH1, beta-catenin/CTNNB1 or gamma-catenin/JUP, and potentially alpha-catenin/CTNNA1; the complex is located to adherens junctions. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1. Interaction with PSEN1, cleaves CDH1 resulting in the disassociation of cadherin-based adherens junctions (CAJs). Interacts with AJAP1, CTNND1 and DLGAP5

By similarity. Interacts with TBC1D2. Interacts with LIMA1. Interacts with CAV1. Interacts with the TRPV4 and CTNNB1 complex

By similarity. Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.25 Ref.26

Subcellular location: Cell junction. Cell membrane; Single-pass type I membrane protein. Endosome. Golgi apparatus � trans-Golgi network. Note: Colocalizes with DLGAP5 at sites of cell-cell contact in intestinal epithelial cells. Anchored to actin microfilaments through association with alpha-, beta- and gamma-catenin. Sequential proteolysis induced by apoptosis or calcium influx, results in translocation from sites of cell-cell contact to the cytoplasm. Colocalizes with RAB11A endosomes during its transport from the Golgi apparatus to the plasma membrane. Ref.4 Ref.18 Ref.21

Tissue specificity: Non-neural epithelial tissues.

Induction: Expression is repressed by MACROD1. Ref.23

Post-translational modification: During apoptosis or with calcium influx, cleaved by a membrane-bound metalloproteinase (ADAM10), PS1/gamma-secretase and caspase-3 to produce fragments of about 38 kDa (E-CAD/CTF1), 33 kDa (E-CAD/CTF2) and 29 kDa (E-CAD/CTF3), respectively. Processing by the metalloproteinase, induced by calcium influx, causes disruption of cell-cell adhesion and the subsequent release of beta-catenin into the cytoplasm. The residual membrane-tethered cleavage product is rapidly degraded via an intracellular proteolytic pathway. Cleavage by caspase-3 releases the cytoplasmic tail resulting in disintegration of the actin microfilament system. The gamma-secretase-mediated cleavage promotes disassembly of adherens junctions. Ref.4 Ref.12 Ref.15N-glycosylation at Asn-637 is essential for expression, folding and trafficking.

Involvement in Disease: Defects in CDH1 are the cause of hereditary diffuse gastric cancer (HDGC) [

MIM:137215]. An autosomal dominant cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Note=Heterozygous germline mutations CDH1 are responsible for familial cases of diffuse gastric cancer. Somatic mutations in the has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer. Ref.36 Ref.41Defects in CDH1 are a cause of susceptibility to endometrial cancer (ENDMC) [

MIM:608089].Defects in CDH1 are a cause of susceptibility to ovarian cancer (OC) [

MIM:167000]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.

Sequence similarities: Contains 5 cadherin domains.

Sequence caution: The sequence AAA61259.1 differs from that shown. Reason: Frameshift at positions 16, 22, 25, 28, 31, 34, 52, 67, 73, 76, 94, 102, 633 and 636.